Background: HD IL-2 has been reported to have a overall response rate (ORR) for mM of 16% and a median OS 11.4 months (Atkins,1999), however, the studies that led to its regulatory approval are >15 years old and were performed in an era predating checkpoint inhibition and targeted therapies. Methods: The PROCLAIM registry (www.proclaimregistry.com), a HD IL-2 observational database currently with over 30 participating sites, consists of a retrospective cohort (treated 2007-2012) informing an ongoing prospective cohort (~600 patients). We report on the retrospective mM subjects (n=170, 11 sites) with survival status determined as of 11/2013 and a median follow-up of 30.5 months. Sites were encouraged to enroll patients sequentially. Inclusion criteria required that patients have received at least one dose of HD IL-2. Results: The ORR for mM in the database was similar to the historical rates. All 170 subjects were accounted for, 98 were deceased and 72 were known to be alive. Median OS was 21 months for mM compared to a median OS range of 6.4-13.6 months for other single agent FDA-approved drugs (Bhatia, 2009; Kaufman, 2005; Hodi, 2010; Chapman, 2012). Among patients with stable disease (SD), median OS was 36.6 months compared to 15.4 months in patients with progressive disease (PD). Median OS has not been reached for patients with complete response (CR) or partial response (PR). Comparison of patients who received HD IL-2 as 1^st or 2^ndline (n=138, 32, respectively) showed no significant difference in OS between these patients. No deaths due to IL-2 related toxicity were reported in the retrospective cohort. Conclusions: The PROCLAIM registry documents an improvement in OS for patients treated with HD IL-2 as compared to the historical reference standards. Response to HD IL-2 traditionally defined as CR or PR and, according to this data, should also include SD, which can be very durable. The observation that 1^st and 2^nd line HD IL-2 possessed similar OS raises intriguing hypotheses about the sequencing of immunotherapy and targeted therapy in mM, and the utility of IL-2 as a salvage option - all of which are currently under examination in the prospective database.